Fibroblast growth factor 21 (FGF21) is a multi-effect endocrine factor, mainly secreted in liver and adipose tissue, with the properties of lipid-lowering, anti-inflammatory, anti-oxidant and anti-atherosclerosis. Recent studies found that FGF21 can induce protective effect in cardiovascular disease, and plasma FGF21 levels in patients with disease cardiovascular are elevated. These studies have suggested the use of FGF21 as a biomarker for subclinical atherosclerosis and its potential role in the treatment of established atherosclerotic cardiovascular disease. This article will review the recent advances in the anti-atherosclerosis effect of FGF21.
Objective To investigate the potential causal associations between 731 immune cell traits and atherosclerosis by Mendelian randomization (MR) analysis. Methods Using single nucleotide polymorphisms (SNPs) as instrumental variables, genome-wide association study (GWAS) summary statistics (GCST90001391 to GCST90002121) for 731 immune cell traits were obtained from the GWAS Catalog database, and the atherosclerosis dataset (finn-b-I9_CORATHER) was retrieved from the IEU database for MR analysis. The inverse variance weighted method, MR-Egger regression, weighted median, simple mode, and weighted mode approaches were employed to estimate the causal effects between the 731 immune cell traits and atherosclerosis, using odds ratio (OR) with 95% confidence interval (CI) as the effect size. Cochran Q test was used to assess heterogeneity. Horizontal pleiotropy was evaluated using the MR-Egger intercept test and the MR-PRESSO method. Leave-one-out analysis was conducted to examine the sensitivity of the causal estimates to individual SNPs. Results MR analysis revealed potential causal associations between 24 immune cell traits and atherosclerosis (P<0.05). Among them, human leucocyte antigen (HLA)-DR on plasmacytoid dendritic cells (DC) [OR=1.035, 95%CI (1.016, 1.054), P<0.001] and hematopoietic stem cell absolute count (HSCAC) [OR=1.049, 95%CI (1.021, 1.077), P<0.001] showed significant positive causal associations with atherosclerosis (P≤0.001), whereas CD86 on CD62L+ myeloid DC [OR=0.953, 95%CI (0.926, 0.981), P=0.001] exhibited a significant negative causal association with atherosclerosis (P≤0.001). The results of Cochran Q test, MR-Egger regression, and MR-PRESSO indicated P-values>0.05, suggesting no evidence of heterogeneity or horizontal pleiotropy in the causal estimates for these three immune cell traits. Reverse MR analysis, using the 24 immune cell traits as outcome variables, showed no evidence of causal association (P>0.05), supporting a unidirectional causal relationship from immune cells to atherosclerosis. Conclusion HLA-DR on plasmacytoid DC and HSCAC may serve as risk factors for atherosclerosis, while CD86 on CD62L+ myeloid DC may play a protective role against atherosclerosis.
ObjectiveTo explore the differential expression of Sirtuin1 (SIRT1) in type A aortic dissection at diverse ages.MethodsThe expression of SIRT1 and monocyte chemoattractant protein-1 (MCP-1) in aortic tissue of the patients with type A aortic dissection (an aortic dissection group) and coronary heart disease (a control group) from 2019 to 2020 in the First Hospital of China Medical University was analyzed. In each group, the patients were divided into 3 subgroups according to the age (a younger subgroup, <45 years; a middle age subgroup, 45-60 years; an elderly subgroup, >60 years). The quantitative real-time PCR, Western blotting and immunochemical stainning were used to detect the mRNA or protein expression of SIRT1 and MCP-1. ResultsA total of 60 patients were included in each group, including 79 males and 41 females. There were 20 patients in the yonger, middle age and elderly subgroups for the two groups, respectively. Compared with the control group, the expression of SIRT1 mRNA decreased in the aortic dissection group (the younger subgroup: 4.54±1.52 vs. 8.78±2.57; the middle age group: 2.70±1.50 vs. 5.74±1.07; the elderly group: 1.41±1.33 vs. 3.09±1.14, P<0.001). Meanwhile, SIRT1 mRNA in the aortic dissection group declined with age (P<0.01). Compared with the control group, SIRT1 protein expression decreased significantly in the aortic dissection group (the younger group: 0.64±0.18 vs. 1.18±0.47; the middle age group: 0.43±0.26 vs. 0.69±0.32; the elderly group: 0.31±0.24 vs. 0.45±0.29, P<0.01). The Western blotting results showed that the expression of SIRT1 protein in the aortic dissection group decreased with age (P<0.01). The MCP-1 protein expression of younger and middle age patients in the aortic dissection group was increased compared with that in the control group (the younger group: 0.65±0.27 vs. 0.38±0.22; the middle age group: 1.08±0.30 vs. 0.46±0.36, P<0.001). MCP-1 expression increased with age (P<0.01). The result of immunohistochemical staining for SIRT1 protein was similar to that of Western blotting.ConclusionThe expression of SIRT1 decreases in patients with aortic dissection disease, and declines with age. SIRT1 may play an important role in the treatment and screening of type A aortic dissection.
Including gut microbiota and oral microbiota, various microorganisms in different human ecosystem constitute the human microbiota, which play an important role in human metabolism, immunity and maintaining microecological homeostasis. Abnormal changes in gut microbiota known as dysbiosis may lead to metabolic abnormalities and inflammatory changes, which are closely related to disease states including hypertension, diabetes, inflammatory bowel disease, and autoimmune diseases. The main cause of coronary artery disease is coronary atherosclerosis, a chronic and progressive inflammatory disease. Many evidences have shown that there is a correlation between gut microbiota and coronary artery disease. Therefore, we aim to review the relationship between gut microbiota and coronary artery disease, and discuss the possible research directions and application prospects.
摘要:目的: 探討動脈硬化閉塞癥(ASO)和靜脈血栓形成(VT)患者同型半胱氨酸(Hcy)變化。 方法 :通過循環酶法對34例非動脈硬化閉塞癥(ASO)和靜脈血栓形成(VT)患者(對照組),30例動脈硬化閉塞癥(ASO)患者和26例靜脈血栓形成(VT)患者血液中Hcy進行測定。 結果 :循環酶法測定HCY的批內平均變異系數為2．23％,批間平均變異系數為1．59％。34例對照組,〖WTBX〗t =1135,〖WTBX〗P =0266gt;005;動脈硬化閉塞癥(ASO)組Hcy含量明顯高于對照組(〖WTBX〗P lt;O．05),靜脈血栓形成(VT)組Hcy含量高于對照組(〖WTBX〗P lt;0．O5)。 結論 :高同型半胱氨酸血癥可能是動脈硬化閉塞癥(ASO)和靜脈血栓形成(VT)及復發的致病因素。可將同型半胱氨酸作為動脈硬化閉塞癥(ASO)和靜脈血栓形成(VT)及復發的重要指標。Abstract: Objective: TO syudy the changes of the Homocysteine about Atherosclerosis obliterans and Venous thrombosis patients. Methods : To measure the Hcy in the blood of 34 healthy cases both non ASO and non VT(the comparison group),30 cases of ASO patients and 26 cases of VT patients respectively by enzymatic cycling assay。〖WTHZ〗Results :The average variation coefficient of Hcy within the groups was 223% and among the groups was 159% measured by enzymatic cycling assay.In the 34 cases of comparison group,t=1135,P=0266gt;005,The content of Hcy in the blood of ASO patients group were significantly higher than the comparision group (Plt;005),and the content of Hcy in the blood of VT patients group were also higher than the comparison group (Plt;005). Conclusion : Hyper Hcy may be the pathogenic diathesis to form or to recrudesce ASO and VT.So we can treat Hcy as the significant index to form or to recrudesce ASO and VT.
ObjectiveTo explore the risk factors affecting occurrence of arteriosclerosis obliterans (ASO) for patients with type 2 diabetes mellitus (T2DM) and to develop a nomogram predictive model using these risk factors. MethodsA case-control study was conducted. The patients with T2DM accompanied with ASO and those with T2DM alone, admitted to the First Affiliated Hospital of Xinjiang Medical University from January 2017 to December 2022, were retrospectively collected according to the inclusion and exclusion criteria. The basic characteristics, blood, thyroid hormones, and other relevant indicators of the paitents in two groups were compared. The multivariate logistic regression analysis was used to identify the risk factors for the occurrence of ASO in the patients with T2DM, and then a nomogram predictive model was developed. ResultsThere were 119 patients with T2DM alone and 114 patients with T2DM accompanied with lower extremity ASO in this study. The significant differences were observed between the two groups in terms of smoking history, white blood cell count, neutrophil count, lymphocyte count, platelet count, systemic immune-inflammation index, systemic inflammatory response index (SIRI), high-density lipoprotein cholesterol, apolipoprotein A1 (ApoA1), apolipoprotein α (Apoα), serum cystatin C, free-triiodothyronine (FT3), total triiodothyronine, FT3/total triiodothyronine ratio, fibrinogen (Fib), fibrinogen degradation products, and plasma D-dimer (P<0.05). Further the results of the multivariate logistic regression analysis revealed that the history of smoking, increased Fib level and SIRI value increased the probabilities of ASO occurrence in the patients with T2DM [OR (95%CI)=2.921 (1.023, 4.227), P=0.003; OR (95%CI)=2.641 (1.810, 4.327), P<0.001; OR (95%CI)=1.020 (1.004, 1.044), P=0.018], whereas higher levels of ApoA1 and FT3 were associated with reduced probabilities of ASO occurrence in the patients with T2DM [OR (95%CI)=0.231 (0.054, 0.782), P=0.021; OR (95%CI)=0.503 (0.352, 0.809), P=0.002]. The nomogram predictive model based on these factors demonstrated a good discrimination for predicting the ASO occurrence in the T2DM patients [area under the receiver operating characteristic curve (95%CI)=0.788 (0.730, 0.846)]. The predicted curve closely matched the ideal curve (Hosmer-Lemeshow goodness-of-fit test, χ2=5.952, P=0.653). The clinical decision analysis curve showed that the clinical net benefit of intervention based on the nomogram model was higher within a threshold probability range of 0.18 to 0.80 compared to no intervention or universal intervention. ConclusionsThe analysis results indicate that T2DM patients with a smoking history, elevated Fib level and SIRI value, as well as decreased ApoA1 and FT3 levels should be closely monitored for ASO risk. The nomogram predictive model based on these features has a good discriminatory power for ASO occurrence in T2DM patients, though its value warrants further investigation.
Obesity, sleep disorders, psychological stress, sedentary are modifiable cardiovascular risk factors. There is growing evidence that these risk factors may accelerate the chronic inflammatory process of atherosclerosis and lead to myocardial infarction. Studies on the role of immune cells and their related immune mechanisms in atherosclerosis have shown that the above modifiable risk factors can affect the hematopoiesis of the bone marrow system, affect the production of immune cells and phenotypes, and then affect the progress of atherosclerosis. This review will focus on the effects of modifiable cardiovascular risk factors on the progression of atherosclerosis through the role of the innate immune system.
ObjectiveTo explore the association of elongase of very long chain fatty acids family member 6 (ELOVL6) gene with increased risk of large-artery atherosclerosis stroke (LAA) in Han Chinese population in Chengdu.MethodsHan Chinese populations in Chengdu, Sichuan were chosen for this study using the case-control design between January 2015 and December 2017. The genotypes and haplotypes of six single nucleotides polymorphisms (SNPs) of ELOVL6 gene (rs3813825, rs17041272, rs4141123, rs9997926, rs6824447, and rs12504538) were analyzed in different genetic models in entire samples, and gene-enviromental interaction analyses were also carried out to get an insight of the risk factors for LAA. At the same time, we also analyzed the gene expression profile in peripheral blood mononuclear cells between groups.ResultsA total of 240 LAA cases and 211 healthy controls were enrolled in this study. All the enrolled subjects presented CC genotype of rs9997926, while the other five SNPs (rs3813825, rs17041272, rs4141123, rs6824447, and rs12504538) were genotyped successfully in all the enrolled subjects. rs17041272 polymorphism and TGTTG haplotype were significantly associated with LAA risk in studied population [CC/(CG+GG): odds ratio (OR)=0.640, 95% confidence interval (CI) (0.423, 0.968), P=0.034; TGTTG: OR=1.776, 95%CI (1.069, 2.951), P=0.024], and the interaction among rs17041272, rs6824447 SNPs and dyslipidemia increased susceptibility to LAA [OR=2.737, 95%CI (1.715, 4.368), P<0.001]. The ELOVL6 gene expression level was higher in LAA subjects (t=?3.167, P=0.003).ConclusionsELOVL6 gene is associated with LAA risk in Han nationality of Chinese population in Chengdu, and the interaction of gene-environmental risk factors could be of great importance in pathophysiology of LAA.
Objective To investigated the influence of the CYP2C9 polymorphism on lipid profile and blood concentration in epileptic children with VPA. Methods This study collected the information of healthy children and epilepsy children who were treated with VPA in the First Affiliated Hospital of Putian University during June, 2018 to March, 2021. The serum lipids of 184 cases were collected and compared between epilepsy group before and after treatment with VPA with the control group. The polymorphism of CYP2C9 gene in children with epilepsy was detected, and lipid and VPA concentration were compared after classification. Results There was no significant difference in lipid between the control group and the epilepsy group before treatment (P>0.05); The TC, HDL, LDL, TC/HDL, LDL/HDL were statistically different in VPA treatment group from the control group (P<0.05), and there were statistical differences in TG, LDL, TC/HDL, LDL/HDL between the trial group before the initiation and VPA treatment (P<0.05); There is no correlation between VPA blood concentration and lipid (P>0.05). VPA concentration, TC, HDL, LDL, TC/HDL and LDL/HDL in CYP2C9 wild-type were statistically different from heterozygous mutant. Conculsions CYP2C9 polymorphism and long-term use of VPA caused the changes in serum lipid levels in epilepsy children.
Atherosclerosis is a complex disease characterized by lipid accumulation in the vascular wall and influenced by multiple genetic and environmental factors. To understand the mechanisms of molecular regulation related to atherosclerosis better, a protein interaction network was constructed in the present study. Genes were collected in nucleotide database and interactions were downloaded from Biomolecular Object Network Database (BOND). The interactional data were imported into the software Cytoscape to construct the interaction network, and then the degree characteristics of the network were analyzed for Hub proteins. Statistical significance pathways and diseases were figured out by inputting Hub proteins to KOBAS2.0. The complete pathway network related to atherosclerosis was constructed. The results identified a series of key genes related to atherosclerosis, which would be the potential promising drug targets for effective prevention.
